Maternal-fetal comorbidities and obstetrical outcomes of fetal single ventricle cardiac defects: 10 years' experience with a multidisciplinary management protocol at a single center.

OBJECTIVES: To describe and compare maternal and fetal comorbidities and obstetrical outcomes in pregnancies with hypoplastic left and right heart (HLHS and HRH) single ventricle cardiac defects (SVCD) from a single center under a multidisciplinary protocol. METHOD: A single center retrospective review of fetal SVCD from 2013 to 2022. Maternal-fetal comorbidities, delivery, and postnatal outcomes were compared between HLHS and HRH using descriptive statistics and univariate and multivariate analyses. RESULTS: Of 181 SVCD pregnancies (131 HLHS; 50 HRH), 9% underwent termination, 4% elected comfort care, 5 died in utero and 147/152 liveborns survived to the first cardiac intervention. Cesarean delivery occurred in 57 cases (37%), planned in 36 and unplanned in 21. Comorbidities, which did not differ between HLHS and HRH, included fetal growth restriction (FGR, 17%), prematurity (14%), maternal hypertension (9%), maternal obesity (50%), fetal extracardiac anomalies and chromosome anomalies (12%, 13%). In multivariate analysis, only earlier gestational age at delivery and oligohydramnios predicted decreased odds of survival at one year. CONCLUSION: Maternal-fetal comorbidities are common in both HLHS and HRH. Earlier gestational age at delivery and oligohydramnios predict lower postnatal survival. FGR, even with severe early onset, did not significantly impact short- or long-term neonatal survival in single ventricle conditions.

Submaximal Exercise Response is Associated with Future Hypertension in Patients with Coarctation of the Aorta.

Hypertension (HTN) is common in patients with a history of coarctation of the aorta (CoA) and remains underrecognized and undertreated. Studies in the non-coarctation otherwise healthy adult population have correlated an exaggerated blood pressure response during mild to moderate exercise with subsequent diagnosis of HTN. The goal of this study was to determine if blood pressure response to submaximal exercise in normotensive CoA patients correlated with development of HTN.Retrospective chart review was performed in individuals ≥ 13 years old with CoA and no diagnosis of HTN at time of cardiopulmonary exercise testing (CPET). Systolic blood pressure (SBP) during CPET at rest, submax 1 (stage 1 Bruce or minute 2 bicycle ramp), submax 2 (stage 2 Bruce or minute 4 bicycle ramp), and peak were recorded. The primary composite outcome was HTN diagnosis or initiation of anti-hypertensive medications at follow up.There were 177 patients (53% female, median age 18.5 years), of whom 38 patients (21%) met composite outcome during a median follow up of 46 months. Men were more likely to develop hypertension. Age at repair and age at CPET were not significant covariates. At each stage of CPET, SBP was significantly higher in those who met the composite outcome. Submax 2 SBP ≥ 145 mmHg was 75% sensitive, 71% specific in males and 67% sensitive, 76% specific in females for development of composite outcome.Our study shows an exaggerated SBP response to submaximal exercise may portend an increased risk of developing hypertension during short- to mid-term follow up.

Anesthesia for Maternal-Fetal Interventions: A Survey of Fetal Therapy Centers in the North American Fetal Therapy Network.

INTRODUCTION: A wide range of fetal interventions are performed across fetal therapy centers (FTCs). We hypothesized that there is significant variability in anesthesia staffing and anesthetic techniques. METHODS: We conducted an online survey of anesthesiology directors at every FTC within the North American Fetal Therapy Network (NAFTNet). The survey included details of fetal interventions performed in 2018, anesthesia staffing models, anesthetic techniques, fetal monitoring, and postoperative management. RESULTS: There was a 92% response rate. Most FTCs are located within an adult hospital and employ a small team of anesthesiologists. There is heterogeneity when evaluating anesthesiology fellowship training and staffing, indicating there is a multidisciplinary specialty team-based approach even within anesthesiology. Minimally invasive fetal interventions were the most commonly performed. The majority of FTCs also performed ex utero intrapartum treatment (EXIT) and open mid-gestation procedures under general anesthesia (GA). Compared to FTCs only performing minimally invasive procedures, FTCs performing open fetal procedures were more likely to have a pediatric surgeon as director and performed more minimally invasive procedures. CONCLUSIONS: There is considerable variability in anesthesia staffing, caseload, and anesthetic techniques among FTCs in NAFTNet. Most FTCs used maternal sedation for minimally invasive procedures and GA for EXIT and open fetal surgeries.

DNA Methylation Changes in Lung Immune Cells Are Associated with Granulomatous Lung Disease.

Epigenetic marks are likely to explain variability of response to antigen in granulomatous lung disease. The objective of this study was to identify DNA methylation and gene expression changes associated with chronic beryllium disease (CBD) and sarcoidosis in lung cells obtained by BAL. BAL cells from CBD (n = 8), beryllium-sensitized (n = 8), sarcoidosis (n = 8), and additional progressive sarcoidosis (n = 9) and remitting (n = 15) sarcoidosis were profiled on the Illumina 450k methylation and Affymetrix/Agilent gene expression microarrays. Statistical analyses were performed to identify DNA methylation and gene expression changes associated with CBD, sarcoidosis, and disease progression in sarcoidosis. DNA methylation array findings were validated by pyrosequencing. We identified 52,860 significant (P < 0.005 and q < 0.05) CpGs associated with CBD; 2,726 CpGs near 1,944 unique genes have greater than 25% methylation change. A total of 69% of differentially methylated genes are significantly (q < 0.05) differentially expressed in CBD, with many canonical inverse relationships of methylation and expression in genes critical to T-helper cell type 1 differentiation, chemokines and their receptors, and other genes involved in immunity. Testing of these CBD-associated CpGs in sarcoidosis reveals that methylation changes only approach significance, but are methylated in the same direction, suggesting similarities between the two diseases with more heterogeneity in sarcoidosis that limits power with the current sample size. Analysis of progressive versus remitting sarcoidosis identified 15,215 CpGs (P < 0.005 and q < 0.05), but only 801 of them have greater than 5% methylation change, demonstrating that DNA methylation marks of disease progression changes are more subtle. Our study highlights the significance of epigenetic marks in lung immune response in granulomatous lung disease.

Estimated Cost Savings: Everyone With Diabetes Counts (EDC) Program.

Everyone with Diabetes Counts (EDC) is a national disparities reduction program funded by the Centers for Medicare & Medicaid Services to improve outcomes in the underserved minority, diverse, and rural populations. This analysis evaluates West Virginia's pilot program of diabetes self-management education (DSME), one component of EDC. We frequency-matched 422 DSME completers to 1688 others by demographics and enrollment from Medicare fee-for service claims. We estimated savings associated with reduced hospitalizations in multivariable negative binomial models. DSME completers had 29% fewer hospitalizations (adjusted P < .0069). We estimated savings of $35 900 per 100 DSME completers in West Virginia.

Beryllium-induced lung disease exhibits expression profiles similar to sarcoidosis.

A subset of beryllium-exposed workers develop beryllium sensitisation (BeS) which precedes chronic beryllium disease (CBD). We conducted an in-depth analysis of differentially expressed candidate genes in CBD.We performed Affymetrix GeneChip 1.0 ST array analysis on peripheral blood mononuclear cells (PBMCs) from 10 CBD, 10 BeS and 10 beryllium-exposed, nondiseased controls stimulated with BeSO4 or medium. The differentially expressed genes were validated by high-throughput real-time PCR in this group and in an additional group of cases and nonexposed controls. The functional roles of the top candidate genes in CBD were assessed using a pharmacological inhibitor. CBD gene expression data were compared with whole blood and lung tissue in sarcoidosis from the Gene Expression Omnibus.We confirmed almost 450 genes that were significantly differentially expressed between CBD and controls. The top enrichment of genes was for JAK (Janus kinase)-STAT (signal transducer and activator of transcription) signalling. A JAK2 inhibitor significantly decreased tumour necrosis factor-α and interferon-γ production. Furthermore, we found 287 differentially expressed genes overlapped in CBD/sarcoidosis. The top shared pathways included cytokine-cytokine receptor interactions, and Toll-like receptor, chemokine and JAK-STAT signalling pathways.We show that PBMCs demonstrate differentially expressed gene profiles relevant to the immunnopathogenesis of CBD. CBD and sarcoidosis share similar differential expression of pathogenic genes and pathways.

Galectin-3 levels are associated with right ventricular functional and morphologic changes in pulmonary arterial hypertension.

The response of the right ventricle (RV) to pulmonary arterial hypertension (PAH) involves changes in contractile function, chamber size, hypertrophy, and extracellular matrix (ECM). Galectin-3 (Gal-3) is a mediator of myocardial ECM metabolism and biomarker for left heart remodeling, yet its ability to reflect RV remodeling is unknown. We hypothesized that serum Gal-3 levels correlate with RV morphology and function in PAH, and that Gal-3 is associated with circulating markers of ECM. Fifteen subjects with PAH and 10 age-matched controls underwent same-day echocardiography, cardiac magnetic resonance (CMR) imaging, and phlebotomy for Gal-3 and ECM biomarkers including N-terminal propeptide of type III collagen type (PIIINP), tissue inhibitor of metalloproteinase-1 (TIMP-1), and hyaluronic acid (HA). RV ejection fraction, end diastolic volume index, end systolic volume index, and mass index were calculated using CMR. Echocardiography was used to estimate RV systolic pressure and measure RV strain. Serum Gal-3, TIMP-1, and HA levels were all significantly increased in PAH subjects when compared to controls. Gal-3 correlated with RV ejection fraction (ρ -0.44, p 0.03), end diastolic volume index (ρ 0.42, p 0.03), end systolic volume index (ρ 0.44, p 0.027), mass index (ρ 0.47, p 0.016), systolic pressure (ρ 0.55, p < 0.001), and strain (ρ 0.43, p 0.03). Gal-3 levels positively correlated with the ECM markers TIMP-1 and HA but not with PIIINP. In conclusion, Gal-3 levels are associated with multiple indices of RV function and morphology. Gal-3 may represent a novel biomarker for RV remodeling and associated ECM turnover in PAH.

Vorticity is a marker of right ventricular diastolic dysfunction.

Right ventricular diastolic dysfunction (RVDD) is an important prognostic indicator in pulmonary arterial hypertension (PAH). RV vortex rings have been observed in healthy subjects, but their significance in RVDD is unknown. Vorticity, the local spinning motion of an element of fluid, may be a sensitive measure of RV vortex dynamics. Using four-dimensional (4D) flow cardiac magnetic resonance imaging (CMR), we investigated the relationship between right heart vorticity with echocardiographic indexes of RVDD. Thirteen (13) PAH subjects and 10 controls underwent same-day 4D flow CMR and echocardiography. RV diastolic function was assessed using trans-tricuspid valve (TV) early (E) and late (A) velocities, E/A ratio, and e' and a' tissue Doppler velocities. RV and right atrial (RA) integrated mean vorticity was calculated for E and A-wave filling periods using 4D datasets. Compared with controls, A-wave vorticity was significantly increased in RVDD subjects in both the RV [2343 (1,559-3,295) vs. 492 (267-2,649) 1/s, P = 0.028] and RA [30 (27-44) vs. 9 (5-27) 1/s, P = 0.005]. RA E vorticity was significantly decreased [13 (7-22) vs. 28 (15-31) 1/s, P = 0.038] in RVDD. E-wave vorticity correlated TV e', E-,and TV E/A (P < 0.05), and A-wave vorticity associated with both TV A and E/A (P < 0.02). RVDD is associated with alterations in E- and A-wave vorticity, and vorticity correlates with multiple echocardiographic markers of RVDD. Vorticity may be a robust noninvasive research tool for the investigation of RV fluid and tissue mechanical interactions in PAH.

Chronic beryllium disease, HLA-DPB1, and the DP peptide binding groove.

Multiple epidemiologic studies demonstrate associations between chronic beryllium disease (CBD), beryllium sensitization (BeS), and HLA-DPB1 alleles with a glutamic acid residue at position 69 (E69). Results suggest that the less-frequent E69 variants (non-*0201/*0202 alleles) might be associated with greater risk of CBD. In this study, we sought to define specific E69-carrying alleles and their amino acid sequences in the DP peptide binding groove, as well as their relationship to CBD and BeS risk, using the largest case control study to date. We enrolled 502 BeS/CBD subjects and 653 beryllium-exposed controls from three beryllium industries who gave informed consent for participation. Non-Hispanic white cases and controls were frequency-matched by industry. HLA-DPB1 genotypes were determined using sequence-specific primer PCR. The E69 alleles were tested for association with disease individually and grouped by amino acid structure using logistic regression. The results show that CBD cases were more likely than controls to carry a non-*02 E69 allele than an *02 E69, with odds ratios (95% confidence interval) ranging from 3.1 (2.1-4.5) to 3.9 (2.6-5.9) (p < 0.0001). Polymorphic amino acids at positions 84 and 11 were associated with CBD: DD versus GG, 2.8 (1.8-4.6), p < 0.0001; GD versus GG, 2.1 (1.5-2.8), p < 0.0001; LL versus GG, 3.2 (1.8-5.6), p < 0.0001; GL versus GG, 2.8 (2.1-3.8), p < 0.0001. Similar results were found within the BeS group and CBD/BeS combined group. We conclude that the less frequent E69 alleles confer more risk for CBD than does *0201. Recent studies examining how the composition and structure of the binding pockets influence peptide binding in MHC genes, as well of studies showing the topology of the TCR to likely bind DPB1 preferentially, give plausible biological rationale for these findings.

Cystatin C: a potential biomarker for pulmonary arterial hypertension.

BACKGROUND AND OBJECTIVE: Cystatin C (CysC), a novel marker of renal function, predicts left heart failure and cardiovascular mortality. The hypothesis that serum CysC levels correlate with right ventricular (RV) morphology, function and pressure in pulmonary arterial hypertension (PAH) was tested. METHODS: As part of a prospective study, 14 PAH subjects and 10 matched controls underwent same-day echocardiography, cardiac magnetic resonance imaging (CMR), and phlebotomy for CysC, brain natriuretic peptide (BNP), and N-terminal BNP (NT-ProBNP). RV ejection fraction (RVEF), end-diastolic volume, end-systolic volume and mass were calculated using CMR. RV systolic pressure (RVSP), strain and diastolic function (including tricuspid valve (TV) E velocity, A velocity, e' velocity, E/A ratio and E/e' ratio) were assessed using echocardiography. RESULTS: RVSP was significantly elevated in PAH subjects versus controls (57 ± 17 vs. 28 ± 8 mm Hg, P < 0.0001). CysC was abnormally elevated in the PAH cohort when compared with controls (1.00 ± 0.23 vs 0.78 ± 0.05 mg/L, P = 0.001). CysC positively correlated with RVSP (rho 0.61, P = 0.002), RV end-diastolic volume (rho 0.50, P = 0.01), RV end-systolic volume (rho 0.58, P = 0.003), mass index (rho 0.66, P = 0.0004), strain (rho 0.51, P = 0.01) and strain rate (rho 0.51, P = 0.01) and negatively correlated with RVEF (rho -0.58, P = 0.003) and TV e' (rho -0.75, P < 0.0001). The same correlations with BNP and NT-ProBNP were comparable with CysC. CONCLUSIONS: In a small cohort, CysC accurately correlates with RV pressure, function and morphology. CysC may represent a novel PAH biomarker.

Bronchoalveolar lavage neuregulin-1 is elevated in acute lung injury and correlates with inflammation.

Shedding of neuregulin (NRG)-1 from the pulmonary epithelium leads to activation of the epithelial human epidermal growth factor receptor (HER)2 receptor, increased pulmonary epithelial permeability and acute lung injury (ALI). We sought to determine whether NRG-1 was detectable and elevated in bronchoalveolar lavage (BAL) and plasma from patients with ALI compared with controls and to determine whether a correlation exists between NRG-1 and inflammation and outcome in ALI. Matched BAL and plasma samples were obtained from 23 ALI patients requiring intubation and mechanical ventilation. Control patients (n=5) included healthy volunteers. NRG-1 and indices of inflammation were measured in BAL and plasma via ELISA. The mean±sd BAL NRG-1 concentration in ALI patients was 187.0±21.35 pg·mL(-1) compared with 85.50±9.2 pg·mL(-1) in controls (p=0.001). Increased BAL NRG-1 was associated with markers of inflammation, and inversely correlated with ventilator-free days (VFDs; r= -0.51, p=0.015). Plasma NRG-1 was elevated in ALI patients compared with controls (611.7±354.2 versus 25.17±19.33 pg·mL(-1), p<0.001) and inversely correlated with VFDs (r= -0.51, p=0.04). These results confirm shedding of NRG-1 in ALI and suggest that the NRG-1-HER2 pathway is active in patients with ALI.

Association between the MUC5B promoter polymorphism and survival in patients with idiopathic pulmonary fibrosis.

IMPORTANCE: Current prediction models of mortality in idiopathic pulmonary fibrosis (IPF), which are based on clinical and physiological parameters, have modest value in predicting which patients will progress. In addition to the potential for improving prognostic models, identifying genetic and molecular features that are associated with IPF mortality may provide insight into the underlying mechanisms of disease and inform clinical trials. OBJECTIVE: To determine whether the MUC5B promoter polymorphism (rs35705950), previously reported to be associated with the development of pulmonary fibrosis, is associated with survival in IPF. DESIGN, SETTING, AND PARTICIPANTS: Retrospective study of survival in 2 independent cohorts of patients with IPF: the INSPIRE cohort, consisting of patients enrolled in the interferon-γ1b trial (n = 438; December 15, 2003-May 2, 2009; 81 centers in 7 European countries, the United States, and Canada), and the Chicago cohort, consisting of IPF participants recruited from the Interstitial Lung Disease Clinic at the University of Chicago (n = 148; 2007-2010). The INSPIRE cohort was used to model the association of the MUC5B genotype with survival, accounting for the effect of matrix metalloproteinase 7 (MMP-7) blood concentration and other demographic and clinical covariates. The Chicago cohort was used for replication of findings. MAIN OUTCOMES AND MEASURES: The primary end point was all-cause mortality. RESULTS: The numbers of patients in the GG, GT, and TT genotype groups were 148 (34%), 259 (59%), and 31 (7%), respectively, in the INSPIRE cohort and 41 (28%), 98 (66%), and 9 (6%), respectively, in the Chicago cohort. The median follow-up period was 1.6 years for INSPIRE and 2.1 years for Chicago. During follow-up, there were 73 deaths (36 GG, 35 GT, and 2 TT) among INSPIRE patients and 64 deaths (26 GG, 36 GT, and 2 TT) among Chicago patients. The unadjusted 2-year cumulative incidence of death was lower among patients carrying 1 or more copies of the IPF risk allele (T) in both the INSPIRE cohort (0.25 [95% CI, 0.17-0.32] for GG, 0.17 [95% CI, 0.11-0.23] for GT, and 0.03 [95% CI, 0.00-0.09] for TT) and the Chicago cohort (0.50 [95% CI, 0.31-0.63] for GG, 0.22 [95% CI, 0.13-0.31] for GT, and 0.11 [95% CI, 0.00-0.28] for TT). In the INSPIRE cohort, the TT and GT genotypes (risk for IPF) were associated with improved survival compared with GG (hazard ratios, 0.23 [95% CI, 0.10-0.52] and 0.48 [95% CI, 0.31-0.72], respectively; P < .001). This finding was replicated in the Chicago cohort (hazard ratios, 0.15 [95% CI, 0.05-0.49] and 0.39 [95% CI, 0.21-0.70], respectively; P < .002). The observed association of MUC5B with survival was independent of age, sex, forced vital capacity, diffusing capacity of carbon monoxide, MMP-7, and treatment status. The addition of the MUC5B genotype to the survival models significantly improved the predictive accuracy of the model in both the INSPIRE cohort (C = 0.71 [95% CI, 0.64-0.75] vs C = 0.68 [95% CI, 0.61-0.73]; P < .001) and the Chicago cohort (C = 0.73 [95% CI, 0.62-0.78] vs C = 0.69 [95% CI, 0.59-0.75]; P = .01). CONCLUSIONS AND RELEVANCE: Among patients with IPF, a common risk polymorphism in MUC5B was significantly associated with improved survival. Further research is necessary to refine the risk estimates and to determine the clinical implications of these findings.

Outbreak of Invasive Group A Streptococcus in Children-Colorado, October 2022-April 2023.

BACKGROUND: In the fall of 2022, we observed a sharp rise in pediatric Invasive Group A Streptococcus (iGAS) hospitalizations in Colorado. We compared the epidemiology, clinical features, and patient outcomes in this outbreak to prior years. METHODS: Between October 2022 and April 2023, we prospectively identified and reviewed iGAS cases in hospitalized pediatric patients at Children's Hospital Colorado. Using laboratory specimen records, we also retrospectively compared the number of patients with sterile site GAS-positive cultures across three time periods: pre-COVID-19 (January 2015-March 2020), height of COVID-19 pandemic (April 2020-September 2022), and outbreak (October 2022-April 2023). RESULTS: Among 96 prospectively identified iGAS cases, median age was 5.7 years old; 66% were male, 70% previously healthy, 39% required critical care, and four patients died. Almost 60% had associated respiratory viral symptoms, 10% had toxic shock syndrome, and 4% had necrotizing fasciitis. Leukopenia, bandemia, and higher C-reactive protein values were laboratory findings associated with need for critical care. There were significantly more cases during the outbreak (9.9/month outbreak vs 3.9/month pre-pandemic vs 1.3/month pandemic), including more cases with pneumonia (28% outbreak vs 15% pre-pandemic vs 0% pandemic) and multifocal disease (17% outbreak vs 3% pre-pandemic vs 0% pandemic), P < .001 for all. CONCLUSIONS: Outbreak case numbers were almost triple the pre-pandemic baseline. The high percentage of cases with associated viral symptoms suggests a link to coinciding surges in respiratory viruses during this time. Invasive GAS can be severe and evolve rapidly; clinical and laboratory features may help in earlier identification of critically ill children.

Risk of chronic beryllium disease by HLA-DPB1 E69 genotype and beryllium exposure in nuclear workers.

RATIONALE: Beryllium sensitization (BeS) and chronic beryllium disease (CBD) are determined by at least one genetic factor, a glutamic acid at position 69 (E69) of the HLA-DPB1 gene, and by exposure to beryllium. The relationship between exposure and the E69 genotype has not been well characterized. OBJECTIVES: The study goal was to define the relationship between beryllium exposure and E69 for CBD and BeS. METHODS: Workers (n = 386) from a U.S. nuclear weapons facility were enrolled into a case-control study (70 BeS, 61 CBD, and 255 control subjects). HLA-DPB1 genotypes were determined by sequence-specific primer-polymerase chain reaction. Beryllium exposures were reconstructed on the basis of worker interviews and historical exposure measurements. MEASUREMENTS AND MAIN RESULTS: Any E69 carriage increased odds for CBD (odds ratio [OR], 7.61; 95% confidence interval [CI], 3.66-15.84) and each unit increase in lifetime weighted average exposure increased the odds for CBD (OR, 2.27; 95% CI, 1.26-4.09). Compared with E69-negative genotypes, a single E69-positive *02 allele increased the odds for BeS (OR, 12.01; 95% CI, 4.28-33.71) and CBD (OR, 3.46; 95% CI, 1.42-8.43). A single non-*02 E69 allele further increased the odds for BeS (OR, 29.54; 95% CI, 10.33-84.53) and CBD (OR, 11.97; 95% CI, 5.12-28.00) and two E69 allele copies conferred the highest odds for BeS (OR, 55.68; 95% CI, 14.80-209.40) and CBD (OR, 22.54; 95% CI, 7.00-72.62). CONCLUSIONS: E69 and beryllium exposure both contribute to the odds of CBD. The increased odds for CBD and BeS due to E69 appear to be differentially distributed by genotype, with non-*02 E69 carriers and E69 homozygotes at higher odds than those with *02 genotypes.

Postoperative Immobilization After Hip Reconstruction in Cerebral Palsy: No Difference Between Hip Spica and Abduction Pillow.

Purpose: This study aims to compare radiographic outcomes and complication rates of immobilization with an abduction pillow to spica casting for postoperative care after a hip reconstruction with varus derotational proximal femur osteotomy (VDRO) with or without pelvic osteotomy for children with cerebral palsy (CP). Methods: 233 children (1-18 years old) diagnosed with CP that underwent VDRO with or without pelvic osteotomy were identified, of which 188 patients were immobilized with a spica cast and 45 were immobilized with an abduction pillow, based on surgeon preference. 123 (65%) in the Spica group and 21 (47%) in the pillow group had pelvic osteotomies. Demographic data and complication rates were collected. Radiographic parameters, including anatomic medial proximal femoral angle (aMPFA), acetabular index (AI) and migration percentage (MP), were measured for each patient at the completion of surgery, six weeks post-operatively, and one year post-operatively. Results: There was not a statistically significant difference in BMI (p = 0.285), gender distribution (p = 0.984), or median follow-up time (p = 0.314) between groups. Rates of complications were consistent among groups with no differences in instances of delayed unions (p = 0.10), subluxations (p = 0.55), infection (p = 0.71), or non-unions (p = 0.10). There was no statistically significant difference in number of patients with an ideal aMPFA, AI, or MP (p = 0.44, p = 0.19, p = 1.00) at one year post-operatively. Conclusions: Immobilization with an abduction pillow is a safe and effective alternative to hip spica casting following hip reconstruction.

A Multicenter Study of Adherence to Best Practices and Application of Epilepsy Quality Metrics in a Pediatric Telemedicine Encounter.

Objective: To assess Epilepsy Quality Metrics (EQM) and guideline implementation in new pediatric patients seen in telemedicine. Methods: Multicenter, cross sectional, retrospective analysis. Results: Patients were similar across 3 centers for age, gender, and insurance type. Eighty-one percent presented for spells. One hundred sixty patients with epilepsy formed the EQM cohort. Results: Seizures described: 95%; frequency: 67%, last seizure documented: 81%, epilepsy syndrome documented: 67%; epilepsy diagnosis: 77%, medications reviewed: 56%, adverse events discussed: 73%. Quality of life discussed: 3%. Anticipatory guidance was described as follows: seizure safety, 57%; driving, 47%; SUDEP, 11%; vitamin D discussion, 19%; pregnancy and folic acid counseling, 4% and 10%. Epileptologists were 4 times as likely as generalists in discussing driving safety (odds ratio 3.93, 95% confidence interval 1.7-8.9; P = .001) for all ages. Significance: Performance on EQM and guideline implementation in pediatric epilepsy telemedicine encounters can be improved.

Cefadroxil Comparable to Cephalexin: Minimum Inhibitory Concentrations among Methicillin-Susceptible Staphylococcus aureus Isolates from Pediatric Musculoskeletal Infections.

Cephalexin and cefadroxil are oral first-generation cephalosporins used to treat methicillin-susceptible Staphylococcus aureus (MSSA) infections. Despite its shorter half-life, cephalexin is more frequently prescribed, although cefadroxil is an appealing alternative, given its slower clearance and possibility for less frequent dosing. We report comparative MIC distributions for cefadroxil and cephalexin, as well as for oxacillin, cephalothin, ceftaroline, and cefazolin, for 48 unique clinical MSSA isolates from pediatric patients with musculoskeletal infections. Both cefadroxil and cephalexin had MIC50 values of 2 µg/mL and MIC90 values of 4 µg/mL. MIC50s for oxacillin, cephalothin, and ceftaroline were ≤0.25 µg/mL, and cefazolin's MIC50 was 0.5 µg/mL. While cefadroxil and cephalexin MICs are higher than those for other active agents, the distributions of MICs for cefadroxil and cephalexin are statistically equivalent, suggesting similar in vitro MSSA activities. Cefadroxil should be further considered an alternative agent to cephalexin, although additional work is needed to identify the optimal dose and frequency of these antibiotics for the treatment of serious MSSA infections. IMPORTANCE Cephalexin and cefadroxil are oral antibiotics that are used to treat serious infections due to the bacteria MSSA. While cephalexin is used more commonly, cefadroxil is excreted from the body more slowly; this generally allows patients to take cefadroxil less frequently than cephalexin. In this study, we compared the abilities of cefadroxil, cephalexin, and several other representative intravenous antibiotics to inhibit the growth of MSSA in the laboratory. Bacterial samples were obtained from children with bone, joint, and/or muscle infections caused by MSSA. We found that cefadroxil and cephalexin inhibited the growth of MSSA at similar concentrations, suggesting similar antibacterial potencies. The selected intravenous antistaphylococcal antibiotics generally inhibited bacterial growth with lower antibiotic concentrations. Based on these results, cefadroxil should be further considered an alternative oral antibiotic to cephalexin, although future research is needed to identify the optimal dose and frequency of these antibiotics for serious infections.

Exposure and genetics increase risk of beryllium sensitisation and chronic beryllium disease in the nuclear weapons industry.

OBJECTIVES: Beryllium sensitisation (BeS) and chronic beryllium disease (CBD) are caused by exposure to beryllium with susceptibility affected by at least one well-studied genetic host factor, a glutamic acid residue at position 69 (E69) of the HLA-DPß chain (DPßE69). However, the nature of the relationship between exposure and carriage of the DPßE69 genotype has not been well studied. The goal of this study was to determine the relationship between DPßE69 and exposure in BeS and CBD. METHODS: Current and former workers (n=181) from a US nuclear weapons production facility, the Y-12 National Security Complex (Oak Ridge, Tennessee, USA), were enrolled in a case-control study including 35 individuals with BeS and 19 with CBD. HLA-DPB1 genotypes were determined by PCR-SSP. Beryllium exposures were assessed through worker interviews and industrial hygiene assessment of work tasks. RESULTS: After removing the confounding effect of potential beryllium exposure at another facility, multivariate models showed a sixfold (OR 6.06, 95% CI 1.96 to 18.7) increased odds for BeS and CBD combined among DPßE69 carriers and a fourfold (OR 3.98, 95% CI 1.43 to 11.0) increased odds for those exposed over an assigned lifetime-weighted average exposure of 0.1 µg/m(3). Those with both risk factors had higher increased odds (OR 24.1, 95% CI 4.77 to 122). CONCLUSION: DPßE69 carriage and high exposure to beryllium appear to contribute individually to the development of BeS and CBD. Among workers at a beryllium-using facility, the magnitude of risk associated with either elevated beryllium exposure or carriage of DPßE69 alone appears to be similar.

Gene-environment interactions influence airways function in laboratory animal workers.

BACKGROUND: Most diseases, including asthma, result from the interaction between environmental exposures and genetic variants. Functional variants of CD14 negatively affect lung function in farm workers and children exposed to animal allergens and endotoxin. OBJECTIVE: We hypothesized that CD14 polymorphisms interact with inhaled endotoxin, mouse allergen, or both to decrease airways function in laboratory animal workers. METHODS: Three hundred sixty-nine Caucasian workers completed a symptom and work exposure questionnaire, skin prick testing, and spirometry. Individual exposure estimates for endotoxin and murine allergen were calculated by weighting task-based breathing zone concentrations by time reported for each task and length of time in the current job. Real-time PCR was used to assess CD14/-1619, -550, and -159 alleles. Multiple linear regression predicting airways function included an interaction term between genotype and exposure. RESULTS: Workers at the highest quartile of the natural log-transformed cumulative endotoxin exposure and with the endotoxin-responsive CD14/-1619 G allele had significantly lower FEV(1) and forced expiratory flow, midexpiratory phase (FEF(25-75)) percent predicted compared with workers with an AA genotype, with no significant differences noted at lower endotoxin levels for either genotype. The gene-environment effect was marked for atopic workers. Laboratory animal allergy, murine allergen exposure, CD14/-159 or -550 genotype, and a gene-exposure interaction term for these genotypes and exposures did not predict changes in lung function. CONCLUSIONS: A significant gene-environment interaction affects airways function in laboratory animal workers. More highly endotoxin-exposed workers with CD14/-1619G alleles have significantly lower FEV(1) and FEF(25-75) percent predicted than those with CD14/-1619AA alleles. Atopic workers are particularly affected by cumulative endotoxin exposures.

IVIG Compared With IVIG Plus Infliximab in Multisystem Inflammatory Syndrome in Children.

OBJECTIVES: To compare initial treatment with intravenous immunoglobulin (IVIG) versus IVIG plus infliximab in multisystem inflammatory syndrome in children (MIS-C). METHODS: Single-center retrospective cohort study of patients with MIS-C who met Centers for Disease Control and Prevention criteria and received treatment from April 2020 to February 2021. Patients were included and compared on the basis of initial therapy of either IVIG alone or IVIG plus infliximab. The primary outcome was need for additional therapy 24 hours or more after treatment initiation. RESULTS: Seventy-two children with MIS-C met inclusion criteria. Additional therapy was needed in 13 of 20 (65%) who received IVIG alone and 16 of 52 (31%) who received IVIG plus infliximab (P = .01). The median (interquartile range) ICU lengths of stay were 3.3 (2.2 to 3.8) and 1.8 (1.1 to 2.1) days, respectively (P = .001). New or worsened left ventricular dysfunction developed in 4 of 20 (20%) and 2 of 52 (4%) (P = .05), and new vasoactive medication requirement developed in 3 of 20 (15%) and 2 of 52 (4%), respectively (P = .13). The median percentage changes in the C-reactive protein level at 24 hours posttreatment compared with pretreatment were 0% (-29% to 66%) and -46% (-62% to -15%) (P < .001); and at 48 hours posttreatment, -5% (-41% to 57%) and -70% (-79% to -49%) respectively (P < .001). There was no significant difference in hospital length of stay, time to fever resolution, vasoactive medication duration, or need for diuretics. CONCLUSIONS: Patients with MIS-C initially treated with IVIG plus infliximab compared with those treated with IVIG alone were less likely to require additional therapy and had decreased ICU length of stay, decreased development of left ventricular dysfunction, and more rapid decline in C-reactive protein levels.